American dentists spend much of their time restoring teeth that have developed secondary (“recurrent”) caries at the margins of previous restorations. It is desirable to provide materials with which to restore teeth esthetically in a manner that will prevent formation of secondary caries caused by separation of restorative materials from tooth surfaces.
Desirably, a dental adhesive bonding material will, upon hardening, possess even higher strength of adhesion to the tooth surfaces than its strength of adhesion to itself (its cohesive strength). When mechanical, or polymerization shrinkage stress from the restorative material cause margin gap formation in the region of the adhesive-tooth interface, the gap should expose two surfaces within the synthetic (and ideally xenobiotic) cross-linked adhesive polymer, rather than a space between the adhesive polymer and the dentin or enamel. Cariogenic bacteria can thrive so long as dentin or enamel surfaces can buffer the acids they excrete, but could not survive within a polymeric enclosure in which their acids would lower the pH to levels below their tolerance.
Many conventional restorative materials and adhesive bonding compositions contain significant quantities of ester groups. The ester groups can be undesirable, in that such groups may become hydrolyzed or saponified in the harsh intraoral environment, especially at or near interfaces of the adhesive bonding compositions and the tooth surfaces. Opening of ester linkages can be catalyzed by acidic or basic aqueous conditions. In aqueous oral environments there are both fluctuations in pH and tensile stresses due to polymerization shrinkage and masticatory activity. Conventional dental resins and composite restorative materials undergo shrinkage during hardening (polymerization) and mechanical stresses from chewing and from thermal changes. Furthermore, human saliva contains esterases that can hydrolyze ester-containing compounds and composites: Finer, Y. Santerre, J. P. (2004), “Salivary esterase activity and its association with the biodegradation of dental composites,” J Dent Res 83(1):22-26; Lee, Y. K., Powers, J. M. (2005), “Influence of salivary organic substances on the discoloration of esthetic dental materials—A review,” J Biomed Mater Res Part B Appl Biomater 76B: 397-402; Lin, B. A., Jaffer, F., Duff, M. D., Tang, Y. W., Santerre, J. P. (2005), “Identifying enzyme activities within human saliva which are relevant to dental resin composite biodegradation,” Biomaterials 4259-4264; and Santerre, J. P., Shajii, L., Tsang, H. (1999), “Biodegradation of commercial dental composites by cholesterol esterase,” J Dent Res 78(8): 1459-1468. When subjected to mechanical stresses or thermal activity of restorative materials, conventional resin bonding agents can separate from the dentin or enamel forming a gap, which allows for “microleakage.” Bacteria can grow in this gap, leading to staining and secondary (“recurrent”) caries formation. Examples of ester-containing compositions are provided in U.S. Pat. No. 5,270,351 Adhesion-promoting agents incorporating polyvalent cations, U.S. Pat. No. 6,583,248 Polymerizable cyclodextrin derivatives, U.S. Pat. No. 6,180,739 Polymerizable cyclodextrin derivatives, U.S. Pat. No. 5,981,740 Polymerizable cyclodextrin derivatives for use in dental applications, U.S. Pat. No. 5,929,131 Polymerizable cyclodextrin derivatives, U.S. Pat. No. 5,910,551 Polymerizable cyclodextrin derivatives, U.S. Pat. No. 5,792,821 Polymerizable cyclodextrin derivatives, and U.S. Pat. No. 5,320,886 Hydrophilic crosslinking monomers and polymers made therefrom.
In some cases, the success of dental adhesive compositions used for bonding by prior and current methodologies is also limited, at least in part, because of partitioning or phase separations of the components as they diffuse into the substrate material: Spencer, P., Wang, Y. (2002), “Adhesive phase separation at the dentin interface under wet bonding conditions,” J Biomed Mater Res 62(3):447-456. This partitioning or phase separation of components, which results from different solubility characteristics of the monomers, initiators, promoters, and other components of the compositions, separates components that must work together for optimal substrate interactions, polymerization, cross-linking, and durability of the adhesive bonding. Also, emphasis in recent research on adhesives for dental applications has been on the use of relatively hydrophobic monomers and their polymers to minimize subsequent water sorption: Tay, F. R., Pashley, D. H., Kapur, R. R., Carrilho, M. R. O., Hur, Y. B., Garrett, L. V., Tay, K. C. Y. (2007), “Bonding BisGMA to dentin—a proof of concept for hydrophobic dentin bonding,” J Dent Res 86(11):1034-1039. Examples of hydrophobic monomers and their polymers are described in Bowen, R. L. (1962): Dental Filling Material Comprising Vinyl Silane Treated Fused Silica and A Binder Consisting of the Reaction Product of Bis Phenol and Glycidyl Acrylate, U.S. Pat. No. 3,066,112; Bowen, R. L. (1965): Method of Preparing a Monomer Having Phenoxy and Methacrylate Groups Linked by Hydroxy Glycerol Groups, U.S. Pat. No. 3,179,623; Bowen, R. L. (1965): Silica-Resin Direct Filling Material and Method of Preparation, U.S. Pat. No. 3,194,783; and Bowen, R. L. (1965): Silica-Resin Direct Filling Material and Method of Preparation, U.S. Pat. No. 3,194,784. The industrial “vinyl ester resins,” believed to have ensued therefrom, and most polyester resins, which polymerize by rapid free-radical mechanisms, do not adhere well to moist surfaces, or to hydrophilic substrates exposed to water. However, many important structural polymers (collagen, cellulose, etc.), minerals (calcium phosphates), and many structural industrial substrates (oxidized or anodized metals or their alloys, hardened cement aggregates, etc.) are hydrophilic and are hydrated when in typical environments. There has been concern expressed in prior art regarding the effects of water sorption: Ito S, et al., 2005, “Effects of resin hydrophilicity on water sorption and changes in modulus of elasticity,” Biomaterials 26:6449-6459. Water sorption into hydrophilic resins (polymers) consisting of chains linked or cross-linked with hydrolyzable ester [—C(═O)O—C—] groups are not expected to be durable in harsh environments for prolonged periods of time. In adhesion-promoting applications, water solubility of the monomeric formulation components is desired to enable penetration, attachment and three-dimensional interlinking with hydrated substrates. This is especially desirable for dental adhesive-bonding compositions, Asmussen, E., Hanson, E. K., Peutzfeldt, A. (1991), “Influence of the solubility parameter of intermediary resin on the effectiveness of the Gluma bonding system,” J Dent Res 70:1290-1293. The concern expressed in prior art regarding water sorption of adhesive polymers, Ito, S., Hashimoto, M., Wadgaonkar, B., Svizero, N., Carvalho, R. M., Yiu, C., Rueggeberg, F. A., Foulger, S., Saito, T., Nishitani, Y., Yoshiyama, M., Tay, F. R., Pashley, D. H. (2005), “Effects of resin hydrophilicity on water sorption and changes in modulus of elasticity,” Biomaterials 26:6449-6459, is related to degradation that can occur from hydrolysis of ester linkages within inadequately cross-linked structures of the prior art polymers.
The prepolymerization components of the dental adhesive bonding material should be sufficiently hydrophilic to penetrate, interlink with and form maximally strong interfacial attractive interactions with the hydrophilic components of tooth structures. The components of the dental adhesive bonding material should be sufficiently compatible with one another and with water to prevent phase separations during countercurrent diffusion into the hydrated asperities of tooth surfaces. The components of the dental adhesive bonding material should not be susceptible to degradation via hydrolysis of ester bonds either before or after polymerization. The components of the dental adhesive bonding material should form a densely cross-linked polymer when hardening in situ.
It would desirable to provide substantially anhydrous monomer formulations that have high solubility parameters of their components to obtain penetration, attachment, and three-dimensional interlinking with the hydrated collagenous assemblages that give strength to tendons, ligaments, bones and teeth, with the micropores of hydrated biological minerals, and with hydrated polysaccharide assemblages that are important in both plant and animal structures, and which formulation components can polymerize to form hydrolytically stable, densely cross-linked polymers. The invention seeks in some embodiments to provide materials with some or all of these properties.